Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification

Takashi Miyazawa, Yoshihiro Ogawa, Hideki Chusho, Akihiro Yasoda, Naohisa Tamura, Yasato Komatsu, Alexander Pfeifer, Franz Hofmann, Kazuwa Nakao

研究成果: Contribution to journalArticle査読

90 被引用数 (Scopus)

抄録

Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2-/- mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2-/- mice differ from CNP-deficient mice (Nppc-/- mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2-/- mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2-/- mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification.

本文言語英語
ページ(範囲)3604-3610
ページ数7
ジャーナルEndocrinology
143
9
DOI
出版ステータス出版済み - 9 2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内分泌学

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